Why Romania as RMS - TOPRA

Agency and industry experience
using one of the Central or Eastern European
Member State as RMS
Daniela Vasilescu
Head of the Bureau for Management of European Procedures
National Medicines Agency, Romania
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TOPICS
1) Choice of RMS; RMS role and Applicant's
duties in DCP/MRP
2) Experience with the procedure and the
RMS; RO experience as RMS and future
expectations
3) Do’s and don’ts (as applicants for a
successful DCP/MRP)
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RMS essential role
in MRP/DCP (1):
- scientific assessor of documentation
- regulatory advisor to the Applicant
- moderator in the discussion between the
Applicant and the CMSs.
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RMS role in MRP/DCP (2)
• has no duty to give a full evaluation of CMSs
comments
• does not classify the importance of CMSs
comments and questions
• has no legal possibility to reject any CMSs
comments provided after the agreed deadlines
(D50, D75, D85 or D100, D145, D205)
• must always be kept informed about Applicant's
proposals to resolve out-standing issues during
MRP/DCP
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APPLICANT`S DUTIES (1)
• to search for a RMS
• to agree on the timetable
• to check and implement all available information
regarding MRP/DCP, science and regulation,
before and during procedure
• to be well informed (!) about any additional
national requirements, e-mail addresses of NCAs
for submission of responses, translations, etc.
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APPLICANT`S DUTIES (2)
• to identify (in advance of MRP/DCP start) any
PSRPH in published CMDh Referrals
• to have one available (!) contact point during
procedure (phone, fax, e-mail); to have an updated
contact detail of ASMF Holder
• to give RMS the required responses (pre-assessment)
in due time
• to produce all responses for invalidation issues and
for comments/questions raised by RMS and CMSs
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APPLICANT`S DUTIES (3)
• to be available for a possible oral explanation in
the CMDh
• to circulate the agreed specifications of drug
substance/product to the RMS and CMSs
• to submit to NCAs accurate translations of the
agreed product information at the End of
Procedure/End of Referral
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Why Romania as RMS - in the
NMA view (1)
• EU Legislation already implemented before the date of
EU accession: Title XVII, The Medicinal Product of Law
95/July 2006 (transposing Directive 2001/83/EC)
• NCA provided with sufficient and professionally well
trained staff able to carry out this activity
• Familiarisation with European legislation and procedures
as early as 1999 in the PERF Program frame and practice
of CADREAC simplified procedures
• NMA experts already actively involved in EMEA/CHMP
WP activities
• Key staff availability to communicate with interested
parties during the entire procedure duration
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Why Romania as RMS - in
the NMA view (2)
• NMA understanding of the need to contribute to
smooth progress of MRP/DCP given the very limited
NCAs number willing to become involved as RMS
(9/30; fully booked until 2010-2011); Letter to HMA
• There is a significant number of medicinal products
for human use manufacturers in Romania (45), who
have expressed their intention to require that Romania
act as RMS for their products
• Romania is an interesting pharmaceutical market (22
million inhabitants and the 7 th largest country in the
EU): at present, almost every newly started procedure
includes Romania as CMS)
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Why Romania as RMS -
in the NMA view (3)
• The NMA has gained a good reputation in the MRP/DCP
procedures having Romania as CMS
• The NMA has gained valuable experience due to the large number of
finalised procedures with Romania as CMS in 20 months after
EU accession: 383 (MRP, DCP, RU)
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Why Romania as RMS - in
the NMA view (4)
NMA assessors are acquainted with and apply in detail
all legal provisions and scientific guidelines in force, so
that the NMA has formulated a rather important
number of comments as CMS
(average: min 11 - max 75) / procedure
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Why Romania as RMS - in
the Applicants view
• the size of Romanian pharmaceutical market (7/30)
• limited availability of other NCAs to act as the RMS
(9/30; fully booked till 2010-2011)
• gained experience of the applicants with NMA
authorization process
• EU Legislation already implemented before accession,
quality of assessment/trained assessors, received LoQ in
finalised or pending MRP/DCP/National procedure
applications)
• MAs already granted in National Procedure ―> MRP
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NMA preparations for acting
as RMS (1)
• establishing the date for starting the process: October 2008
• establishing of type of products to be accepted in the first
instance taking into account NMA experience:
10. 1 applications of RPs which have not been authorised
through CP
• identifying of assessors (6 assessors + PTL)
• NMA Team study visit at MPA, April 2008
• official announcement of HMA and CMDh (starting with
October 2008)
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NMA preparations for acting
as RMS (2)
• intention announcement and template to be filled - posted
on www.anm.ro from October 2007 (1 year in advance of
first started procedure as RMS);
• NMA prerequisites for allocation the number of procedure:
inside of the NMA purpose, type of product/INN, slot time
asked according to the NMA availability, NMA gained
experience as CMS; electronic dossier checked by the
NMA in advance of Day -14
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Types of requests received
for Romania as RMS
• simple questions about the first slot time
• requests out of the NMA published scope: RP
authorised through CP; 10.b, 10a, 10.3
applications
• 10.1 requests without sufficient detailed
information (dossier still in preparation, BE ongoing,
without any information about GCP
inspected BE site, manufacturing sites outside
EEA)
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Types of requests received
(150) for Romania as RMS
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NMA SOP for decision to act
as RMS (1)
• monthly NMA top management meetings for
acceptance/refusal of requests, followed by
NMA response for each received request -
usually in 30 days)
• in case of a positive decision, pre-submission
meeting with the Applicant
• 4 months in advance of Day -14 NMA request
for electronic MAA: check of legal base, RP,
comparative SPCs of RPs authorised in
proposed CMSs, PhV System, RMP, BE studies
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NMA SOP for decision to act
as RMS (2)
• NMA first consolidated LoQ (6 assessors +
PTL) sent to the Applicant
• NMA receiving of answers to LoQ
• allocation of number of procedure:
RO/H/10X/…
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Current situation (before
September 1 st , 2008)
• Total requests: 150; Accepted requests: 14
• NMA positive answer: (MRP = 4; DCP = 10)
• One MRP or DCP will be started every month
• Fully booked to January 2009
• 2 DCPs pre-assessed: many quality inconsistencies
(AP and RP of ASMF), different approved SPC
of RP indicating a PSRPH, statement for
Module 1.3.4 to be performed during clock-stop,
Module 1.8.1 not ready yet)
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Critical DCP/MRP issues
for both NCA/Applicant (1)
• expired data exclusivity
• MA of RP not according to Acquis Communeautaire
• NCAs and CMDh advice before starting a procedure
• in force BPGs, SOPs, ICH Guidelines, NfG on BE, CMDh
Recommendations, HBD List, not included in MAA
• MAA requirements (copies, originally signed documents,
e-CTD); updated information according to monthly News
published on the HMA/CMDh website: www.hma.eu
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Critical DCP/MRP issues
for both NCA/Applicant (2)
• submission of application in due time (Day -14); fees to be
paid (in advance of submission in RO)
• GMP, GLP, GCP compliance at Day -14/Day 106
• weak points of submitted MAA (validated process on
commercial batches, incomplete stability studies, another BE
study); availability of Applicant's responses; potential Plan B
• legal base chosen according to current situation of RP in
MSs (10.1; 10.2; 10.3)
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Critical DCP/MRP issues
for both NCA/Applicant (3)
• good communication of RMS with involved CMSs
• available contact person of Applicant and ASMF
Holder
• invented name checked in advance
• known agreed efficacy and safety issues of
proposed INN – see finalised CMDh/CHMP
Referrals; is there a PSRPH
• possibility of withdrawal, CMDh oral explanation,
Applicant's commitment(s)
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Critical DCP/MRP issues for
both NCA/Applicant (4)
• high-quality translations well in advance of End
of procedure (submitted to NCA within 5 days after
End of procedure)
• planned variations due to changes/commitments
immediately after End of procedure (after 30 days
National phase, provided that high quality
translations have been submitted to all involved
CMSs)
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Can a Referral be avoided
• Statistics of Referrals: BE, lack of SPC harmonisation,
Quality, Regulatory issues
• Applicant: very well informed in advance, flexible in
discussions with RMS, very well trained staff, pertinent
response/justifications in case of a raised PSRPH
• RMS: careful assessment of a PSRPH, high quality ARs,
correct interpretations of Guidelines, experience gained
from other completed procedures of the same INN, finalised
CMDh Referrals, CHMP Referrals, CHMP WP decisions
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Present circumstances to obtain
a slot for Romania as RMS
• filled templates submitted with all required details
• applications in accordance with NMA published
conditions
• electronic dossier ready to be submitted in advance
• applications for medicinal products containing INN
for which NMA is experienced enough
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NMA expectations
• successfully finalised procedures with Romania as
RMS for 10.1 applications without or limited
number of Referrals
• increased ability to cooperate with CMSs during
procedures
• one procedure/month to be started
• increased speed of assessment
• increased number of experienced clinical assessors
inside the NMA
• extension of NMA scope acting as RMS
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Do`s:
• carefully read the HMA/CMDh/NCAs website
• give complete available details for any potential question of
selected NCA acting as RMS;
• give complete and very well prepared answers to any
potential delayed CMSs questions during procedure
• be constructive and flexible for reaching the final target
• have a Plan B in place for certain issues
• be well prepared for possible oral explanation/commitments
• provide high quality translation within 5 days after End
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Don`ts:
• keep insufficiently informed on regulatory/scientific aspects
of your MAA
• submit incompletely developed MAA
• submit delayed responses during procedure
• assail the RMS with minor questions
• minimise any RMS concern regarding the proposed/ongoing
procedure
• be unavailable as a PTL at key days of procedure
• be inflexible to any RMS/CMSs proposals
• submit poor quality and delayed translations
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Questions
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Thank you for your attention !
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